Additive antifibrotic effects of pioglitazone and candesartan on experimental renal fibrosis in mice

ABSTRACT Aim: To examine the additive protective effects of the peroxisome proliferator‐activated receptor‐γ agonist pioglitazone (Pio) and the angiotensin II receptor blocker candesartan (Cand) in a murine model of renal fibrosis: mice with unilateral ureteral obstruction (UUO). Methods: Mice were randomly assigned into four groups that after UUO received i.p. injections of either Pio (10 mg/kg/day), Cand (1 mg/kg/day), Cand + Pio or vehicle for 10 days. Physiological parameters, the degree of renal fibrosis and molecules related to renal fibrosis were analysed, and sham‐operated mice were used as controls. Results: Total collagen assay showed prominent renal fibrosis in the vehicle‐treated mice, significantly attenuated renal fibrosis in the Cand‐treated and the Pio‐treated mice, and further attenuated renal fibrosis in the (Cand + Pio)‐treated mice. Real‐time reverse transcription polymerase chain reaction revealed that this attenuation pattern was also evident in the expression of the mRNA for transforming growth factor‐β, collagens I and III, and plasminogen activator inhibitor‐1. Conclusion: Pioglitazone and candesartan have additive protective effects on renal fibrosis due to UUO in mice, suggesting that their use in combination would be an effective treatment for chronic kidney disease. This paper shows that the combination of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) agonists and candesartan in a non‐diabetic model of experimental renal fibrosis is associated with an additive effect. Although lacking in mechanism, this paper has important implications for the potential use of PPAR‐γ agonists as antifibrotic therapies in non‐diabetic renal disease.